In general, biological sample collection and analysis techniques are well known. Clinical patient samples are commonly collected for morphological, chemical, cellular and/or molecular analyses. Diagnostic analyses may be performed on whole blood and whole tissue samples, or such samples may be processed to separate the fractions or components of interest prior to analysis. Sample analysis is also performed to analyze the safety and efficacy of therapeutic treatments, and to monitor a patient's condition during ongoing treatment. Access to well characterized patient samples is essential for research and for development of new diagnostic and therapeutic agents and techniques.
Peripheral blood samples are used for many diagnostic purposes and are generally easier and less intrusive to collect than whole tissue samples. The paradigm for biomarker detection in peripheral blood for the detection of various conditions is based on the assumption that important biological factors within tissue enter the blood and can be detected peripherally. Peripheral blood contains low levels of many cellular and molecular markers, however, and detection of many markers using blood samples is difficult due to the low level of markers present in peripheral blood circulation.
Various types of biological tissue samples are therefore sampled, or biopsied, for research and diagnosis, and many types of tissue sampling and biopsy devices are available. Needle-type biopsy devices and endoscopic biopsy devices are well known, for example. Tissue is also collected during invasive or minimally invasive procedures, such as collection of plaque from blood vessels during an atherectomy or plaque excision procedure, for later analysis. Tissue samples generally provide a more probative biological sample than peripheral blood samples, but they also require specialized handling techniques.
Plaque from patients suffering from cardiovascular or peripheral vascular disease may be collected as a strand or as particles carried in a liquid, such as aspirate removed from the site of an intervention. Plaque collection techniques using a plaque excision device that collects plaque as a strand are described, for example, in U.S. Patent Publications 2003/0120295A1; 2003/0125757A1; 2005/0222519A1; 2005/0177068 A1; and 2005/0222663 A1.
Aspirating atherectomy and thrombectomy devices that remove and withdraw plaque and disease tissue from blood vessels are also well known. Filtration devices for use in filtering aspirate collected during a plaque removal procedure have been described, for example, in U.S. Pat. Nos. 5,938,645 and 5,827,229, and in U.S. Patent Publication No. 2006/0270974 A1. One of the challenges in filtering aspirate collected in real time during an interventional procedure is clogging of the filter, which disrupts aspirate collection and may consequently delay or disrupt the interventional procedure. Multiple filter assemblies and/or unfiltered by-pass flow paths have been proposed to avoid interruption of the procedure. The present invention, in one aspect, is directed to providing effective real-time aspirate filtration while avoiding clogging of filtration elements that may interrupt or delay the procedure.
Biological materials are generally sensitive to degradation when exposed to conditions that are different from in situ conditions. Many tissue components decompose and denature, for example, upon exposure to ambient temperatures and conditions following removal from the body. For this reason, biological samples are often chilled or frozen soon after removal from a subject, and some sample preparation techniques, such as centrifugation, are carried out under low temperature conditions. In some cases, entire experimental protocols are carried out in a cold room to prevent degradation of biological materials. Sample collection techniques such as filtration techniques, however, do not generally involve a cooling process unless the filtration is carried out in a cold room. The present invention, in another aspect, is directed to preventing degradation of biological samples during a filtration process.